Bidirectional Two-Sample, Two-Step Mendelian Randomisation Study Reveals Mediating Role of Gut Microbiota Between Vitamin B Supplementation and Alzheimer's Disease.

Objectives: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with a complex aetiology. The aims of this study were to investigate the relationship between vitamin B supplementation and AD risk and to explore the potential mediating effect of the gut microbiota in this relationship.
Methods: We employed a Mendelian randomisation analysis to examine the association between different vitamin B supplementation modalities (vitamin B ₆ , folic acid, B ₁₂ , and vitamin B complex tablets) and AD risk. Univariate Mendelian randomisation with inverse-variance weighting was used. Additionally, mediation analyses were conducted to identify the potential mediating effects of 119 known bacterial genera.
Results: The univariate Mendelian randomisation analyses showed no significant direct associations between individual vitamin B supplements or vitamin B complex tablets and AD risk. However, several gut bacterial genera were significantly associated with AD risk. Lachnospiraceae (NK4A136 group), Paraprevotella, Slackia, and Bifidobacterium were associated with reduced AD risk, while Defluviitaleaceae (UCG011), Desulfovibrio , Eubacterium ventriosum group, and Ruminococcaceae UCG-003 were associated with increased AD risk. The mediation analysis revealed that Lachnospiraceae (NK4A136 group), Defluviitaleaceae (UCG011), and Bifidobacterium fully mediated the causal relationships between vitamin B ₁₂ , B ₆ , and B complex supplementation, respectively, and AD risk.
Conclusions: This study provides evidence suggesting that certain gut microbiota genera are significantly associated with AD risk and may mediate the relationship between vitamin B supplementation and AD risk. These findings offer new insights into the variable effectiveness of B vitamins in treating neurodegenerative diseases and suggest potential new strategies for AD treatment and prevention.